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INDIA-LAC INTERNATIONAL PHARMA MEET

JUNE 2007, HYDERABAD

Se t t in g St a n da r ds for D ie t a r y
Su pple m e n t s & e n a blin g st a n da r ds
compliance
Kumud Sampath
Vice President-International
United States Pharmacopeia - India
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2007 U.S. P

All rights reserved U.S.P.C.

2007

Agenda

USP

A BRIEF OVERVIEW

DIETARY SUPPLEMENTS DEFINITION,


LEGALITY & REGULATION
USP DIETARY SUPPLEMENT STANDARDS
USP STRENGTHENING BOTANICAL
STANDARDS
DIETARY SUPPLEMENTS
VERIFICATION

THE NEED FOR USP

USP

A BRIEF OVERVIEW

USP Mission

USP promotes the public health by


establishing and disseminating officially
recognized standards of quality and
authoritative information for the use of
medicines and other health care technologies
by health professionals, patients, and
consumers.

What is USP

Established in 1820 by Lyman Spaulding


Mission is to protect public health by
establishing public standards
Independent; not for profit science based
Standard setting organization
Unique volunteer based organization
Convention meets every five years in
Washington, D.C. (2005)
Headquartered in Rockville, MD

What USP does


Through a unique & open Public process USP;
Establishes Public Standards for drug
substances, drug products, excipients &
Dietary supplements
Establishes General test Methods,definitions
& Information
Supplies Reference Standards to enable
analytical tests for Standards compliance

USP

International Presence

Towards carrying forward its Mission of Public


Health USP is reaching out Globally;

European Office started in 2005 at Basel, Switzerland


USP-India Estabished & Started operations in 2006
USP-China Established & Start operations in 2007
USP-Brazil Site approved by Board of Trustees & is
slated to start operations 2008

Objectives of USP International


Operations
Work closely with the Regional Industry & with
Regulators & other stakeholders
Involve the Regional Pharmaceutical Industry in the
Standard Setting Process
Offer USP Verification Services to the Industry & other
Stakeholders
Increase awareness of & availability of USP s
Pharmacopeial products and services like Reference
Standards & Pharmacopeial Education Courses etc.
Establish collaborative testing Lab for Reference
Standard candidate material
Enlist regional pharmaceutical scientists in Council of
Experts
Facilitate structured information exchange through
Scientific Meetings
USP 7 th ASM
I n dia w ill be
held in February 2008 at Hyderabad

DIETARY SUPPLEMENTS DEFINITION,


LEGALITY & REGULATION

The Legality

Dietary Supplements Health and Education


Act (DSHEA) was Enacted by the U.S.
Congress in October 1994

DSHEA Recognizes the USP Standards for


Dietary Supplements.

What is a Dietary Supplement?

Dietary Supplement as per DSHEA


is a product that is intended to supplement
the diet and contains one or more of the
following dietary ingredients: a vitamin, a
mineral, an herb or other botanical, an
amino acid, a dietary substance for use by
man to supplement the diet by increasing
the total daily intake, or a concentrate,
metabolite, constituent, extract, or
combinations of these ingredients.

USP Standards

Official Recognition

Federal Food, Drug, and Cosmetic Act


Sections 201 (g) and (j), 501(b), 502(g)
USP and NF standards FDA enforceable for all drugs.
Conformance is generally not optional and is enforced by FDA

Dietary Supplement Health & Education


Act (DSHEA)

Section 403(s)(2)(D) of the FD&C Act


A dietary supplement represented as conforming to USP
NF specifications shall be deemed misbranded if it fails to
do so.

Conformance is optional, but enforceable by


FDA

USP DIETARY SUPPLEMENT STANDARDS

USP & D ie t a r y Su pple m e n t St a n da r ds

USP s tryst with


Dietary
Supplements
started way back
in 1820 when it
published
standards for
natural medicines
in the first
Pharmacopoeia

Historical Perspective

1820- 1900

USP s standards
compendium included only
natural medicines. e.g.
Chamomile, Valerian, and
Ginger

1820- 1940

USP developed over


600 botanical
monographs

1942

1990

USP
monographs for
single
ingredient
vitamins and
minerals

USP adopted a
resolution to
expand
monograph
development
for vitamins
and minerals

Tim e line of USP on D ie t a r y Su pple m e n t s


Publication
1995

2003

In response to DSHEA,
USP explored the
feasibility of establishing
standards and information
for botanical and nonbotanical Dietary
Supplements with a GMP
General Chapter

USP 27 NF 22 includes a
separate dietary supplements
section with more than 200
monographs for botanicals,
nonbotanicals, and vitaminmineral combination products
used in nearly 900 dietary
supplement products.

2008

USP D ie t a r y Su pple m e n t M onogr a ph s

DS Type
Test
Identity

Purity

Quality

Content

Vitamin

Minerals

IR, HPLC RT,


UV, Chemical
Chromatographic
purity, Limit
Tests, Microbial,
Heavy Metals

Chemical

Packaging,
Labeling,
Uniformity.
Dissolution,
Disintegration
Spectroscopy,
HPLC, Microbial

Packaging,
Labeling,
Uniformity,
Dissolution,
Disintegration
AA, ICP,
Titration

Non
Botanicals

IR, HPLC RT,


UV, Chemical
Chemical Limit Chrom. purity,
tests, Limit of
Limit Tests,
foreign metals Microbial,
by AA, ICP
Heavy Metals,
PCBs-Dioxins
Packaging,
Labeling,
Uniformity,
Dissolution,
Disintegration
Spectroscopy,
HPLC,
Titration

Botanicals
Microscopy, TLC,
HPLC, GC
Toxins, Aflatoxins,
Heavy Metals,
Pesticides, Foreign
Matter, Residue On
Ignition, Microbial,
Negative Markers
Packaging, Labeling,
Extractable Matter,
Uniformity,
Dissolution,
Disintegration
HPLC, GC

USP

STRENGTHENING BOTANICAL
STANDARDS

USP - Strengthening Botanical Standards

Top selling Botanicals (Journal of American Botanical Council, 2004)


Garlic
Echinacea
Saw Palmetto
Ginkgo
Soy
Cranberry
Ginseng
Black Cohosh
St. John s wort
Milk thistle

Evening primrose
Valerian
Green tea
Bilberry
Grape seed
Horny goat weed
Yohimbe
Horse Chestnut
Eleuthero
Ginger

USP - Strengthening Botanical Standards

Recently Established USP Standards


Black Cohosh
Soy Isoflavones
Turmeric
Green Tea Extract
Bilberry Extract
Senna pods

USP Standards at different stages of development


Grape seeds extract
Boswellia oleo-gum resin
Fenugreek seeds
Spirulina blue green algae
Guggul oleo-gum resin
Ashwaganda roots

Articles for which USP seeks to Establish Standards on Priority


-

Aloe vera gel


Cinnamon bark
Passionflower flowering and fruiting tops
Elderberry flowers and berries
Mangosteen fruits
Reishi mushrooms
Noni fruits - Black currant oil
Stevia leaves

Cranberry fruit extract


Linseed oil
Olive leaves
Borage oil
Artichoke leaves and flower heads
Pau d arco bark

- Shiitake mushrooms

USP - Strengthening Botanical Standards


Criteria for Consideration of Articles Proposed for Placement
in the USP-NF
1.Human data: safety studies, clinical studies, postmarketing surveillance, adverse events, interactions,
publicly available data
2.Pharmacological data: including reproductive toxicity,
experimental animal studies, pharmacokinetics,
therapeutic index, presence of toxic constituents
3. Contemporaneous extent of use globally and in the
U.S.; including misuse and abuse and taking into
account fluctuations of use; historical use,
5.Regulatory status in the U.S. and other countries:
regulatory actions, OTC status, GRAS status, etc.
6.Existence of Official Pharmacopeial Monographs

USP - Strengthening Botanical Standards

USP Dietary Supplement General Chapters relevant to


Botanicals;
<563> IDENTIFICATION OF ARTICLES OF BOTANICAL ORIGIN
<565> BOTANICAL EXTRACTS
<2021> MICROBIAL ENUMERATION TESTS-NUTRITIONAL AND
DIETARY SUPPLEMENTS
<2022> MICROBIOLOGICAL PROCEDURES FOR ABSENCE OF
SPECIFIED MICROORGANISMS-NUTRITIONAL AND DIETARY
SUPPLEMENTS
<2023> MICROBIOLOGICAL ATTRIBUTES OF NONSTERILE
NUTRITIONAL AND DIETARY SUPPLEMENTS
<2030> SUPPLEMENTAL INFORMATION FOR ARTICLES OF
BOTANICAL ORIGIN
<2040> DISINTEGRATION AND DISSOLUTION OF DIETARY
SUPPLEMENTS
<2091> WEIGHT VARIATION OF DIETARY SUPPLEMENTS
<2750> MANUFACTURING PRACTICES FOR DIETARY
SUPPLEMENTS

USP - Strengthening Botanical Standards

Revisions to General Chapters & New General


Chapters under consideration;
The use of polymerase chain reactions (PCR) in
botanical identification.
The use of electron microscopy in botanical
identification.
Bioassay of the antioxidant activity of dietary
supplements including botanicals.
Revision to the pesticides testing in the USP General
Chapter <561>, Articles of Botanical Origin.
Heavy metals in botanicals limits and testing
procedures for individual heavy metals.

USP - Strengthening Botanical Standards

Collaboration with the Indian Stakeholders


MOU with Indian Pharmacopoeia
Commission
MOU with PHARMEXCIL
R&D alliances with Industry & Institutions

DIETARY SUPPLEMENTS THE NEED FOR


USP VERIFICATION

All Su pple m e n t s Ar e N ot Cr e a t e d Equ a l !

All Su pple m e n t s Ar e N ot Cr e a t e d Equ a l !


27 multivitamin / multi-mineral products tested

9 failed

1 prenatal vitamin had only 75% and 1


multi had only 50% of its claimed amount
of folic acid
2 products had less than 40% of their
labeled amount of beta-carotene, 1 had excessive amounts
1 product failed to disintegrate
The remaining failures either had excess
or were deficient in labeled content
A study of Coenzyme Q10 showed
that consumers could go from
175% to 0% of the labeled amount
by simply changing brands

All Su pple m e n t s Ar e N ot Cr e a t e d Equ a l !

Recent survey of 10 herbs in 20 retail


stores showed;
A total of 880 products
37% were deficient in labeling information

92 products for Echinacea (27 brands)


Strengths on product labels varied by a factor
of five

42 products for Goldenseal (15 brands)


Strengths on product labels varied by a factor
of twenty
J. Garrard et al, Arch Inter Med, 163 p.2290.

All Su pple m e n t s Ar e N ot Cr e a t e d Equ a l !

Routine problems associated with Dietary


Supplement Ingredients;
Failure to meet an assay consistently
Failure to meet a minimum impurity profile consistently
Failure to meet GMP requirements
Heavy metals and pesticide contamination
Microbial contamination
Adulterated materials

USP I n gr e die n t Ve r ifica t ion Pr ogr a m s


A Public Health opportunity
Increased Regulatory pressure in most countries for
imports & for dosage form manufacturers
Increasing risk in global supply chain
Hyper-competitive market drives need to visibly
demonstrate quality
Liability remains high for high-margin markets, driving
need for quality assurance can help reduce risk
Trending towards uniformity in quality standards will
allow for independent certification to serve multiple
purposes

USP s Verification Products


For Dietary Supplement
Finished Products
For Dietary Supplement
Ingredients
For Pharmaceutical
Ingredients, including Drug
Substances and Excipients

USP Ve r ifie d D ie t a r y Su pple m e n t s

The USP Verified Mark means:


What s on the label is in the bottle.
The supplement does not contain harmful
levels of contaminants.
The supplement will break down
properly to allow ingredients
to dissolve in your body.
The supplement has been
made under safe, sanitary,
manufacturing
processes.

Cu st om e r s use USP t o show qu a lit y

USP Dietary Supplement Ingredient


Verification
Ingredients covered by this program
Vitamins
Minerals
Amino acids
Powdered botanicals and botanical extracts
Non- botanical dietary supplements covered
by DSHEA and legally marketed in the U.S. (e.g.
fish oil, chondroitin sulfate sodium, glucosamine,
etc.)
Excipients

USP Dietary Supplement Ingredient


Verified Mark

Th e USP Ve r ifie d M a r k m e a n s:
Pre-audit documentation
On-site GMP audit

approved

approved

Quality control documentation

approved

Manufacturing documentation

approved

Drug substance samples tested

approved

Sigma- tau HealthScience advertisement


for the USP Verified Ingredients

USP Pharmaceutical Ingredient


Verification
Ingredients covered by this program
Drug substances used in the manufacture of
pharmaceutical products

Excipients

USP Pharmaceutical Ingredient


Verified Mark

Th e USP Ve r ifie d M a r k m e a n s:
Pre-audit documentation
On-site GMP audit

approved

approved

Quality control documentation

approved

Manufacturing documentation

approved

Drug substance samples tested

approved

The Verification Process

1. Guidelines
from USP
Expert
Committees

6. Surveillance
test of product
using the mark

5. Review of
conformance
with mark
usage
guidelines

2. Audit of
manufacturing
sites for GMP
compliance
3. Review of
documentation
manufacturing,
QA, QC

4. Laboratory
testing of
product
samples

The Verification Benefit

Succesful conclusion of the


Ve r ifica t ion pr oce ss w ill e n t it le
the Client to;
Certificate of Standards Compliance
valid for 3- years
Right to use the USP Verified mark on
the Ingredient/ Product packaging &
on the certificate of Analysis

The Value of USP Verification

For ingredient producers


Demonstrate the quality of your product
Differentiate your product from others
Show that you meet world class quality requirements
Earn preferred supplier status with brokers, distributors,
and manufacturers
For distributors, brokers, and finished product
manufacturers
Reduce the risk of inconsistent and sub-standard quality
from suppliers
Reduce the time and effort needed to qualify incoming
product
Reduce the likelihood that ingredients will be rejected and
must be returned

The Value of USP Verification

Benefits for Regulatory authorities


Promote the public health
Build on Extended regulatory capacities
Reduce the regulatory burden by creating a
common review and audit function in participating
countries
Get the assurance of USP, a name associated with
Quality & recognized world-wide and working as
an independent, science based organization driven
by its mission for ensuring Good Pharmaceutical
care for all

USP India

Contact Information

Address:
ICICI Knowledge Park
Genome Valley
Turkapally
Shameerpet
Hyderabad 500 078
Tel: 40-2348-0088
Fax: 40-2348-0089
Contacts:
Kumud Sampath
Vice President-International, India
Email: KXS@usp.org
A.V. Murali Krishna
Customer Relationship Manager
E-mail: AVM@usp.org